Matsumoto Takayuki, Kobayashi Tsuneo, Kamata Katsuo
Deparment of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Am J Physiol Heart Circ Physiol. 2003 Jul;285(1):H283-91. doi: 10.1152/ajpheart.00954.2002.
In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18alpha-glycyrrhetinic acid (18alpha-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF-type responses were very similar in magnitude between diabetic and age-matched control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3-selective inhibitor, but not by Ro 20-1724, a PDE4-selective inhibitor. The expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were significantly increased in STZ-induced diabetic rats, but those for PDE4D were not. We conclude that the impairment of EDHF-type relaxations in STZ-induced diabetic rats may be attributed to a reduction in the action of cAMP via increased PDE activity.
在来自年龄匹配的对照大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠的离体肠系膜上动脉环中，我们研究了环磷酸腺苷（cAMP）在内皮衍生超极化因子（EDHF）型舒张中的作用。在STZ诱导的糖尿病大鼠中，乙酰胆碱（ACh）诱导的EDHF型舒张明显弱于对照大鼠，并且在两组大鼠中，它均被缝隙连接抑制剂18α-甘草次酸（18α-GA）减弱，并被cAMP磷酸二酯酶（PDE）抑制剂异丁基甲基黄嘌呤（IBMX）增强。糖尿病大鼠和年龄匹配的对照大鼠之间，这些增强的EDHF型反应在幅度上非常相似。EDHF型舒张被PDE3选择性抑制剂西洛他唑增强，但未被PDE4选择性抑制剂Ro 20-1724增强。在STZ诱导的糖尿病大鼠中，两种cAMP PDE（PDE3A、PDE3B）的mRNA和蛋白表达水平显著增加，但PDE4D的表达水平未增加。我们得出结论，STZ诱导的糖尿病大鼠中EDHF型舒张功能受损可能归因于PDE活性增加导致cAMP作用减弱。
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